Brief Summary
In this study, participants with metastatic triple negative breast cancer (mTNBC) will be randomly assigned to receive either single agent pembrolizumab or single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines, consisting of either capecitabine, eribulin, gemcitabine, or vinorelbine. The primary study hypothesis is that pembrolizumab extends overall survival compared to TPC.
Brief Title
Study of Single Agent Pembrolizumab (MK-3475) Versus Single Agent Chemotherapy for Metastatic Triple Negative Breast Cancer (MK-3475-119/KEYNOTE-119)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Metastatic Triple Negative Breast Cancer
Eligibility Criteria
Inclusion Criteria:
* Centrally confirmed Stage IV/M1 mTNBC
* Newly obtained tumor biopsy from metastatic site
* Central determination of programmed cell death ligand 1 (PD-L1) tumor status
* Received either one or two prior systemic treatments for metastatic breast cancer and have documented disease progression on or after the most recent therapy
* Previously treated with an anthracycline and/or taxane in the neoadjuvant/adjuvant or metastatic setting
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
* Adequate organ function
Exclusion Criteria:
* Participation in another clinical trial within 4 weeks
* Monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks
* Chemotherapy, targeted small molecule therapy, or radiation therapy within at least 2 weeks
* Active autoimmune disease that required systemic treatment in the past 2 years
* Diagnosed with immunodeficiency or receiving systemic steroid therapy or another form of immunosuppressive therapy within 7 days
* Known additional malignancy that required treatment or progressed in last 5 years
* Known active brain metastases and/or carcinomatous meningitis
* Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand-1 (anti-PD-L1), anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte associated protein 4 \[CTLA-4\], OX-40, CD137) or previously participated in any pembrolizumab (MK-3475) clinical studies
* Centrally confirmed Stage IV/M1 mTNBC
* Newly obtained tumor biopsy from metastatic site
* Central determination of programmed cell death ligand 1 (PD-L1) tumor status
* Received either one or two prior systemic treatments for metastatic breast cancer and have documented disease progression on or after the most recent therapy
* Previously treated with an anthracycline and/or taxane in the neoadjuvant/adjuvant or metastatic setting
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
* Adequate organ function
Exclusion Criteria:
* Participation in another clinical trial within 4 weeks
* Monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks
* Chemotherapy, targeted small molecule therapy, or radiation therapy within at least 2 weeks
* Active autoimmune disease that required systemic treatment in the past 2 years
* Diagnosed with immunodeficiency or receiving systemic steroid therapy or another form of immunosuppressive therapy within 7 days
* Known additional malignancy that required treatment or progressed in last 5 years
* Known active brain metastases and/or carcinomatous meningitis
* Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand-1 (anti-PD-L1), anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte associated protein 4 \[CTLA-4\], OX-40, CD137) or previously participated in any pembrolizumab (MK-3475) clinical studies
Inclusion Criteria
Inclusion Criteria:
* Centrally confirmed Stage IV/M1 mTNBC
* Newly obtained tumor biopsy from metastatic site
* Central determination of programmed cell death ligand 1 (PD-L1) tumor status
* Received either one or two prior systemic treatments for metastatic breast cancer and have documented disease progression on or after the most recent therapy
* Previously treated with an anthracycline and/or taxane in the neoadjuvant/adjuvant or metastatic setting
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
* Adequate organ function
* Centrally confirmed Stage IV/M1 mTNBC
* Newly obtained tumor biopsy from metastatic site
* Central determination of programmed cell death ligand 1 (PD-L1) tumor status
* Received either one or two prior systemic treatments for metastatic breast cancer and have documented disease progression on or after the most recent therapy
* Previously treated with an anthracycline and/or taxane in the neoadjuvant/adjuvant or metastatic setting
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
* Adequate organ function
Gender
All
Gender Based
false
Keywords
Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02555657
Org Class
Industry
Org Full Name
Merck Sharp & Dohme LLC
Org Study Id
3475-119
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Randomized Open-Label Phase III Study of Single Agent Pembrolizumab Versus Single Agent Chemotherapy Per Physician's Choice for Metastatic Triple Negative Breast Cancer (mTNBC) - (KEYNOTE-119)
Primary Outcomes
Outcome Description
Overall survival (OS) was defined as the time from randomization to death due to any cause.
Outcome Measure
Overall Survival in Participants With Programmed Cell Death Ligand 1 (PD-L1) With Combined Positive Score (CPS) ≥10
Outcome Time Frame
Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Outcome Description
Overall survival (OS) was defined as the time from randomization to death due to any cause.
Outcome Measure
Overall Survival in Participants With PD-L1 CPS ≥1
Outcome Time Frame
Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Outcome Description
Overall survival (OS) was defined as the time from randomization to death due to any cause.
Outcome Measure
Overall Survival in All Participants
Outcome Time Frame
Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Secondary Ids
Secondary Id
2015-001020-27
Secondary Id
153082
Secondary Id
MK-3475-119
Secondary Id
KEYNOTE-119
Secondary Outcomes
Outcome Description
Overall Response Rate (ORR), based on a Blinded Independent Central Review (BICR) assessment per RECIST 1.1, was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions).
Outcome Time Frame
Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Outcome Measure
Overall Response Rate Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With PD-L1 CPS ≥10
Outcome Description
Overall Response Rate (ORR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions).
Outcome Time Frame
Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Outcome Measure
Overall Response Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1
Outcome Description
Overall Response Rate (ORR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions).
Outcome Time Frame
Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Outcome Measure
Overall Response Rate Per RECIST 1.1 in All Participants
Outcome Description
Progression-Free Survival (PFS), based on BICR assessment per RECIST 1.1, was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Outcome Time Frame
Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Outcome Measure
Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥10
Outcome Description
Progression-Free Survival (PFS), based on BICR assessment per RECIST 1.1, was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Outcome Time Frame
Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Outcome Measure
Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥1
Outcome Description
Progression-Free Survival (PFS), based on BICR assessment per RECIST 1.1, was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Outcome Time Frame
Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Outcome Measure
Progression-Free Survival Per RECIST 1.1 in All Participants
Outcome Description
For participants with PD-L1 CPS ≥10 who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR.
Outcome Time Frame
Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019)
Outcome Measure
Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 Who Had a Confirmed Response
Outcome Description
For participants with PD-L1 CPS ≥1 who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR.
Outcome Time Frame
Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019)
Outcome Measure
Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 Who Had a Confirmed Response
Outcome Description
For participants who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR.
Outcome Time Frame
Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019)
Outcome Measure
Duration of Response Per RECIST 1.1 in All Participants Who Had a Confirmed Response
Outcome Description
Disease Control Rate (DCR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease for at least 24 weeks (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.\])
Outcome Time Frame
Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Outcome Measure
Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥10
Outcome Description
Disease Control Rate (DCR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease for at least 24 weeks (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.\])
Outcome Time Frame
Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Outcome Measure
Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1
Outcome Description
Disease Control Rate (DCR), based on BICR assessment per RECIST 1.1, was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease for at least 24 weeks (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.\])
Outcome Time Frame
Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Outcome Measure
Disease Control Rate Per RECIST 1.1 in All Participants
Outcome Description
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Outcome Time Frame
Up to approximately 60 months
Outcome Measure
Number of Participants Who Experienced One or More Adverse Events
Outcome Description
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Outcome Time Frame
Up to approximately 60 months
Outcome Measure
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Joseph Sparano
Investigator Email
jsparano@montefiore.org
Investigator Phone
718-405-8404